ArticleHuman molecular genetics2011
Xpa deficiency reduces CAG trinucleotide repeat instability in neuronal tissues in a mouse model of SCA1.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- CAG repeat mosaicism is gene specific in spinocerebellar ataxias.American journal of human genetics · 2024Article
- Article
- Elevated glucose increases genomic instability by inhibiting nucleotide excision repair.Life science alliance · 2021Article
- Modifiers of Somatic Repeat Instability in Mouse Models of Friedreich Ataxia and the Fragile X-Related Disorders: Implications for the Mechanism of Somatic Expansion in Huntington's Disease.Journal of Huntington's disease · 2021Review
- Modifiers of CAG/CTG Repeat Instability: Insights from Mammalian Models.Journal of Huntington's disease · 2021Review
- Patterns of CAG repeat instability in the central nervous system and periphery in Huntington's disease and in spinocerebellar ataxia type 1.Human molecular genetics · 2020Article
- A point mutation in the nuclease domain of MLH3 eliminates repeat expansions in a mouse stem cell model of the Fragile X-related disorders.Nucleic acids research · 2020Article
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
- Large-scale contractions of Friedreich's ataxia GAA repeats in yeast occur during DNA replication due to their triplex-forming ability.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias.Frontiers in neuroscience · 2020Review
- Dysfunctional DNA repair pathway via defective FANCD2 gene engenders multifarious exomic and transcriptomic effects in Fanconi anemia.Molecular genetics & genomic medicine · 2018Article
- Genetic instability associated with loop or stem-loop structures within transcription units can be independent of nucleotide excision repair.Nucleic acids research · 2018Article
- Article
- The central role of DNA damage and repair in CAG repeat diseases.Disease models & mechanisms · 2018Review
- Close encounters: Moving along bumps, breaks, and bubbles on expanded trinucleotide tracts.DNA repair · 2017Review
- RNA toxicity and foci formation in microsatellite expansion diseases.Current opinion in genetics & development · 2017Review
- Mechanisms of DNA damage, repair, and mutagenesis.Environmental and molecular mutagenesis · 2017Review
- Age-related length variability of polymorphic CAG repeats.DNA repair · 2017Article
- The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington's disease.Mechanisms of ageing and development · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Expansion of trinucleotide repeats (TNRs) is responsible for a number of human neurodegenerative disorders. The molecular mechanisms that underlie TNR instability in humans are not clear. Based on results from model systems, several mechanisms for instability have been proposed, all of which focus on the ability of TNRs to form alternative structures during normal DNA transactions, including replication, DNA repair and transcription. These abnormal structures are thought to trigger changes in TNR length. We have previously shown that transcription-induced TNR instability in cultured human cells depends on several genes known to be involved in transcription-coupled nucleotide excision repair (NER). We hypothesized that NER normally functions to destabilize expanded TNRs. To test this hypothesis, we bred an Xpa null allele, which eliminates NER, into the TNR mouse model for spinocerebellar ataxia type 1 (SCA1), which carries an expanded CAG repeat tract at the endogenous mouse Sca1 locus. We find that Xpa deficiency does not substantially affect TNR instability in either the male or female germline; however, it dramatically reduces CAG repeat instability in neuronal tissues-striatum, hippocampus and cerebral cortex-but does not alter CAG instability in kidney or liver. The tissue-specific effect of Xpa deficiency represents a novel finding; it suggests that tissue-to-tissue variation in CAG repeat instability arises, in part, by different underlying mechanisms. These results validate our original findings in cultured human cells and suggest that transcription may induce NER-dependent TNR instability in neuronal tissues in humans.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.